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href=\u0022\/\/cdn.jsdelivr.net\/qtip2\/2.2.1\/jquery.qtip.min.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022https:\/\/www.bmj.com\/sites\/default\/files\/advagg_css\/css__GkPSKUkdJ2bzIT9BLdob0bbh88SFHg9JxcNgbdHlbDc__qYTxeL-KKGqFiuvt1Pd7tJWAZkcDxAZN7jCKDHxZcE0__b2e6faiQ_UWIrIhhy-1_GBi9M1f1xMsmWzx8NA2PKwk.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-jnl-bmj-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n \n \n \n \u003Cdiv class=\u0022pane-content\u0022\u003E\n \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 data-highwire-cite-ref-tooltip-instance=\u0022highwire_reflinks_tooltip\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view\u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022contributors\u0022\u003E\u003Col class=\u0022contributor-list\u0022 id=\u0022contrib-group-1\u0022\u003E\u003Cli class=\u0022contributor\u0022 id=\u0022contrib-1\u0022\u003E\u003Cspan class=\u0022name\u0022\u003EJulia Hippisley-Cox\u003C\/span\u003E\u003Cspan class=\u0022contrib-role\u0022\u003E, professor of clinical epidemiology and general practice\u003C\/span\u003E, \u003C\/li\u003E\u003Cli class=\u0022last\u0022 id=\u0022contrib-2\u0022\u003E\u003Cspan class=\u0022name\u0022\u003ECarol Coupland\u003C\/span\u003E\u003Cspan class=\u0022contrib-role\u0022\u003E, associate professor in medical statistics\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Col class=\u0022affiliation-list\u0022\u003E\u003Cli class=\u0022aff\u0022\u003E\u003Ca id=\u0022aff-1\u0022 name=\u0022aff-1\u0022\u003E\u003C\/a\u003E\u003Caddress\u003E\u003Csup\u003E1\u003C\/sup\u003EDivision of Primary Care, University Park, Nottingham NG2 7RD\u003C\/address\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Col class=\u0022corresp-list\u0022\u003E\u003Cli class=\u0022corresp\u0022 id=\u0022corresp-1\u0022\u003ECorrespondence to: J Hippisley-Cox \u003Cspan class=\u0022em-link\u0022\u003E\u003Cspan class=\u0022em-addr\u0022\u003Ejulia.hippisley-cox{at}ntlworld.com\u003C\/span\u003E\u003C\/span\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003Cul class=\u0022history-list\u0022\u003E\u003Cli xmlns:hwp=\u0022http:\/\/schema.highwire.org\/Journal\u0022 class=\u0022accepted\u0022 hwp:start=\u00222010-03-02\u0022\u003E\u003Cspan class=\u0022accepted-label\u0022\u003EAccepted \u003C\/span\u003E2 March 2010\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003EAbstract\u003C\/h2\u003E\u003Cp id=\u0022p-2\u0022\u003E\u003Cstrong\u003EObjective\u003C\/strong\u003E To quantify the unintended effects of statins according to type, dose, and duration of use.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003E\u003Cstrong\u003EDesign\u003C\/strong\u003E Prospective open cohort study using routinely collected data.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003E\u003Cstrong\u003ESetting\u003C\/strong\u003E 368 general practices in England and Wales supplying data to the QResearch database.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003E\u003Cstrong\u003EParticipants\u003C\/strong\u003E 2\u2009004\u2009692 patients aged 30-84 years of whom 225\u2009922 (10.7%) were new users of statins: 159\u2009790 (70.7%) were prescribed simvastatin, 50\u2009328 (22.3%) atorvastatin, 8103 (3.6%) pravastatin, 4497 (1.9%) rosuvastatin, and 3204 (1.4%) fluvastatin.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003E\u003Cstrong\u003EMethods\u003C\/strong\u003E Cox proportional hazards models were used to estimate effects of statin type, dose, and duration of use. The number needed to treat (NNT) or number needed to harm (NNH) was calculated and numbers of additional or fewer cases estimated for 10\u2009000 treated patients.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003E\u003Cstrong\u003EMain outcome measure\u003C\/strong\u003E First recorded occurrence of cardiovascular disease, moderate or serious myopathic events, moderate or serious liver dysfunction, acute renal failure, venous thromboembolism, Parkinson\u2019s disease, dementia, rheumatoid arthritis, cataract, osteoporotic fracture, gastric cancer, oesophageal cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003E\u003Cstrong\u003EResults\u003C\/strong\u003E Individual statins were not significantly associated with risk of Parkinson\u2019s disease, rheumatoid arthritis, venous thromboembolism, dementia, osteoporotic fracture, gastric cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer. Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataract. Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin. A dose-response effect was apparent for acute renal failure and liver dysfunction. All increased risks persisted during treatment and were highest in the first year. After stopping treatment the risk of cataract returned to normal within a year in men and women. Risk of oesophageal cancer returned to normal within a year in women and within 1-3 years in men. Risk of acute renal failure returned to normal within 1-3 years in men and women, and liver dysfunction within 1-3 years in women and from three years in men. Based on the 20% threshold for cardiovascular risk, for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 (95% confidence interval 27 to 64) and for oesophageal cancer was 1266 (850 to 3460) and for men the respective values were 33 (24 to 57) and 1082 (711 to 2807). In women the NNH for an additional case of acute renal failure over five years was 434 (284 to 783), of moderate or severe myopathy was 259 (186 to 375), of moderate or severe liver dysfunction was 136 (109 to 175), and of cataract was 33 (28 to 38). Overall, the NNHs and NNTs for men were similar to those for women, except for myopathy where the NNH was 91 (74 to 112).\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003E\u003Cstrong\u003EConclusions\u003C\/strong\u003E Claims of unintended benefits of statins, except for oesophageal cancer, remain unsubstantiated, although potential adverse effects at population level were confirmed and quantified. Further studies are needed to develop utilities to individualise the risks so that patients at highest risk of adverse events can be monitored closely.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022source-body\u0022\u003E\u003Cdiv class=\u0022section intro\u0022 id=\u0022intro\u0022\u003E\u003Ch2\u003EIntroduction\u003C\/h2\u003E\u003Cp id=\u0022p-10\u0022\u003ECardiovascular disease is the leading cause of premature death and a major cause of disability in the United Kingdom.\u003Ca id=\u0022xref-ref-1-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-1\u0022\u003E1\u003C\/a\u003E Some meta-analyses and national policies support the use of statins to reduce the risk of cardiovascular disease among high risk patients.\u003Ca id=\u0022xref-ref-2-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003E2\u003C\/a\u003E \u003Ca id=\u0022xref-ref-3-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-3\u0022\u003E3\u003C\/a\u003E \u003Ca id=\u0022xref-ref-4-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-4\u0022\u003E4\u003C\/a\u003E \u003Ca id=\u0022xref-ref-5-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-5\u0022\u003E5\u003C\/a\u003E Validated risk prediction algorithms, such as QRISK2, are used to identify high risk patients most likely to benefit from interventions, including statins.\u003Ca id=\u0022xref-ref-6-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-6\u0022\u003E6\u003C\/a\u003E \u003Ca id=\u0022xref-ref-7-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-7\u0022\u003E7\u003C\/a\u003E Given that statins are already among the most widely prescribed medicines and that their use is likely to continue to increase, both their intended and their unintended effects and how these vary by type, dose, and duration of use need to be quantified in large representative populations. This information can then be used to inform policy and clinical practice by supplementing information from meta-analyses of clinical trials, which tend to lack sufficient detail, duration of follow-up, or sufficient power to make some of the relevant comparisons.\u003Ca id=\u0022xref-ref-2-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003E2\u003C\/a\u003E \u003Ca id=\u0022xref-ref-3-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-3\u0022\u003E3\u003C\/a\u003E \u003Ca id=\u0022xref-ref-5-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-5\u0022\u003E5\u003C\/a\u003E \u003Ca id=\u0022xref-ref-8-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-8\u0022\u003E8\u003C\/a\u003E \u003Ca id=\u0022xref-ref-9-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-9\u0022\u003E9\u003C\/a\u003E Also, meta-analyses can be subject to selection bias as trial patients tend to be predominantly white, younger, and more healthy than real world populations, thus limiting generalisability and external validity.\u003Ca id=\u0022xref-ref-8-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-8\u0022\u003E8\u003C\/a\u003E\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EWe carried out a large population based study to examine a range of clinical outcomes that have been found to be positively or negatively associated with statin use, including moderate or serious myopathic events,\u003Ca id=\u0022xref-ref-10-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-10\u0022\u003E10\u003C\/a\u003E \u003Ca id=\u0022xref-ref-11-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-11\u0022\u003E11\u003C\/a\u003E \u003Ca id=\u0022xref-ref-12-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-12\u0022\u003E12\u003C\/a\u003E \u003Ca id=\u0022xref-ref-13-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-13\u0022\u003E13\u003C\/a\u003E Parkinson\u2019s disease,\u003Ca id=\u0022xref-ref-14-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-14\u0022\u003E14\u003C\/a\u003E dementia,\u003Ca id=\u0022xref-ref-15-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-15\u0022\u003E15\u003C\/a\u003E \u003Ca id=\u0022xref-ref-16-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-16\u0022\u003E16\u003C\/a\u003E liver dysfunction,\u003Ca id=\u0022xref-ref-8-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-8\u0022\u003E8\u003C\/a\u003E \u003Ca id=\u0022xref-ref-9-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-9\u0022\u003E9\u003C\/a\u003E \u003Ca id=\u0022xref-ref-17-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-17\u0022\u003E17\u003C\/a\u003E venous thromboembolism,\u003Ca id=\u0022xref-ref-18-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-18\u0022\u003E18\u003C\/a\u003E rheumatoid arthritis,\u003Ca id=\u0022xref-ref-19-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-19\u0022\u003E19\u003C\/a\u003E cataract,\u003Ca id=\u0022xref-ref-20-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-20\u0022\u003E20\u003C\/a\u003E common cancers,\u003Ca id=\u0022xref-ref-9-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-9\u0022\u003E9\u003C\/a\u003E \u003Ca id=\u0022xref-ref-21-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-21\u0022\u003E21\u003C\/a\u003E \u003Ca id=\u0022xref-ref-22-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-22\u0022\u003E22\u003C\/a\u003E \u003Ca id=\u0022xref-ref-23-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-23\u0022\u003E23\u003C\/a\u003E \u003Ca id=\u0022xref-ref-24-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-24\u0022\u003E24\u003C\/a\u003E and osteoporotic fracture.\u003Ca id=\u0022xref-ref-25-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-25\u0022\u003E25\u003C\/a\u003E \u003Ca id=\u0022xref-ref-26-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-26\u0022\u003E26\u003C\/a\u003E \u003Ca id=\u0022xref-ref-27-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-27\u0022\u003E27\u003C\/a\u003E We also included acute renal failure as an outcome because of concerns published both in \u003Cem\u003EThe Lancet\u003C\/em\u003E\u003Ca id=\u0022xref-ref-28-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-28\u0022\u003E28\u003C\/a\u003E and on the Food and Drug Administration website,\u003Ca id=\u0022xref-ref-29-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-29\u0022\u003E29\u003C\/a\u003E together with reports of proteinuria in patients prescribed rosuvastatin.\u003Ca id=\u0022xref-ref-30-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-30\u0022\u003E30\u003C\/a\u003E\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section methods\u0022 id=\u0022methods\u0022\u003E\u003Ch2\u003EMethods\u003C\/h2\u003E\u003Cp id=\u0022p-12\u0022\u003EWe carried out a prospective cohort study in a large population of primary care patients using version 24 of the general practice research database, QResearch. All practices in England and Wales that had been using the computer based Egton Medical Information System (EMIS) for at least a year were included. Two thirds of the practices were randomly allocated to the study dataset and one third was retained for a subsequent study. We identified an open cohort of patients aged 30-84 years from those registered with the practices between 1 January 2002 and 30 June 2008. We excluded patients without a postcode related Townsend score (about 4% of the population) and those who had been prescribed statins before, or were current users on, the date the study started. Entry to the cohort was the latest of the date the study started, 12 months after the patient registered with the practice, or, for new users of statins, the date of their first prescription. We censored patients at the earliest date of the diagnosis of interest, death, deregistration with the practice, last upload of computerised data, or the date the study ended (31 December 2008).\u003C\/p\u003E\u003Cdiv id=\u0022sec-3\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003EClinical outcomes\u003C\/h3\u003E\u003Cp id=\u0022p-13\u0022\u003EWe examined several outcomes, identified from Read codes recorded in the patients\u2019 electronic records (codes available from authors on request): acute renal failure\u003Ca id=\u0022xref-ref-28-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-28\u0022\u003E28\u003C\/a\u003E \u003Ca id=\u0022xref-ref-30-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-30\u0022\u003E30\u003C\/a\u003E; venous thromboembolism\u003Ca id=\u0022xref-ref-18-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-18\u0022\u003E18\u003C\/a\u003E; Parkinson\u2019s disease\u003Ca id=\u0022xref-ref-14-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-14\u0022\u003E14\u003C\/a\u003E; dementia\u003Ca id=\u0022xref-ref-15-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-15\u0022\u003E15\u003C\/a\u003E \u003Ca id=\u0022xref-ref-16-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-16\u0022\u003E16\u003C\/a\u003E; rheumatoid arthritis\u003Ca id=\u0022xref-ref-19-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-19\u0022\u003E19\u003C\/a\u003E; cataract\u003Ca id=\u0022xref-ref-20-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-20\u0022\u003E20\u003C\/a\u003E; osteoporotic fracture (spine, hip, or wrist); common cancers (gastric, colon, oesophageal, lung, renal, breast, prostate, melanoma); moderate or severe liver dysfunction, defined as an alanine transaminase concentration \u0026gt;120 IU\/l (that is, more than three times the upper limit of normal) among patients without diagnosed chronic liver disease, as this is the severity at which guidelines recommend treatment is discontinued\u003Ca id=\u0022xref-ref-9-4\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-9\u0022\u003E9\u003C\/a\u003E \u003Ca id=\u0022xref-ref-31-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-31\u0022\u003E31\u003C\/a\u003E; and moderate or serious myopathic events,\u003Ca id=\u0022xref-ref-9-5\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-9\u0022\u003E9\u003C\/a\u003E \u003Ca id=\u0022xref-ref-10-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-10\u0022\u003E10\u003C\/a\u003E \u003Ca id=\u0022xref-ref-11-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-11\u0022\u003E11\u003C\/a\u003E \u003Ca id=\u0022xref-ref-12-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-12\u0022\u003E12\u003C\/a\u003E \u003Ca id=\u0022xref-ref-13-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-13\u0022\u003E13\u003C\/a\u003E \u003Ca id=\u0022xref-ref-32-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-32\u0022\u003E32\u003C\/a\u003E which for our study was defined as a diagnosis of myopathy or rhabdomyolysis or a raised creatine kinase concentration of four or more times the upper limit of normal, as this represents an event where treatment is likely to be discontinued.\u003C\/p\u003E\u003Cdiv id=\u0022sec-4\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EPredictor and exposure variables\u003C\/h4\u003E\u003Cp id=\u0022p-14\u0022\u003EWe identified new users of statins during the study period, with the remaining patients classified as non-users. To correspond to an intention to treat analysis we classified statin use by type of statin first prescribed (atorvastatin, simvastatin, fluvastatin, pravastatin, or rosuvastatin). We examined starting dose using categories similar to those published elsewhere,\u003Ca id=\u0022xref-ref-33-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-33\u0022\u003E33\u003C\/a\u003E \u003Ca id=\u0022xref-ref-34-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-34\u0022\u003E34\u003C\/a\u003E collapsing categories when data were insufficient to support analysis. We compiled a list of potential predictor variables, which included established risk factors for each outcome from the literature or existing risk prediction scores, using similar definitions when possible.\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-5\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003EStatistical modelling\u003C\/h3\u003E\u003Cp id=\u0022p-15\u0022\u003ETo estimate the hazard ratios for each outcome for type of statin first prescribed for men and women separately, we used Cox proportional hazards models to compare new users with non-users, adjusting for potential confounding variables. So that we considered first events only we excluded patients from the analysis of each outcome when they had a diagnosis of the outcome at or before the baseline date. We used multiple imputation to replace missing values for body mass index and smoking status and used these values in our main analyses.\u003Ca id=\u0022xref-ref-35-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-35\u0022\u003E35\u003C\/a\u003E \u003Ca id=\u0022xref-ref-36-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-36\u0022\u003E36\u003C\/a\u003E \u003Ca id=\u0022xref-ref-37-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-37\u0022\u003E37\u003C\/a\u003E \u003Ca id=\u0022xref-ref-38-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-38\u0022\u003E38\u003C\/a\u003E We carried out five imputations. When appropriate we used fractional polynomials to model non-linear risk relations with continuous variables.\u003Ca id=\u0022xref-ref-39-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-39\u0022\u003E39\u003C\/a\u003E When we found significant associations for individual statins we examined the effects of dose. We tested for interactions between statin use and age and between smoking and deprivation and included significant interactions in the final models. We carried out two global tests; one to check that there was no overall effect of individual statins, and, if that test gave significant results a test for equality of effects of individual statins. When the hazard ratio was less than 0.80 or greater than 1.20 and was statistically significant at the 0.01 level we considered the effect of statins to be significant.\u003C\/p\u003E\u003Cdiv id=\u0022sec-6\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003ETime varying analyses\u003C\/h4\u003E\u003Cp id=\u0022p-16\u0022\u003EWhen associations for individual statins were significant, we used a time varying Cox regression analysis to examine the effects of duration of use and time since stopping any statin. We examined statins overall and by type. To determine the risk of each outcome within a year, 1-3 years, 3-5 years, and five or more years of taking statins we compared non-users with new users. We also determined change in risks after stopping statins, categorised as stopping treatment within a year, 1-3 years, and three or more years. The date of stopping statins was taken to be 90 days after the date of the last recorded prescription.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-7\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003ESelf controlled case series analysis\u003C\/h4\u003E\u003Cp id=\u0022p-17\u0022\u003EIn addition, we undertook post hoc self controlled case series analyses for the significant outcomes other than cancer. The case series methodology was originally developed to assess adverse events to vaccination\u003Ca id=\u0022xref-ref-40-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-40\u0022\u003E40\u003C\/a\u003E but has a wider application.\u003Ca id=\u0022xref-ref-41-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-41\u0022\u003E41\u003C\/a\u003E \u003Ca id=\u0022xref-ref-42-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-42\u0022\u003E42\u003C\/a\u003E \u003Ca id=\u0022xref-ref-43-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-43\u0022\u003E43\u003C\/a\u003E It can be used to determine the relative incidence of the outcome of interest for periods of drug use compared with periods of non-use in people with the outcome of interest. Inference is within individuals and hence implicitly controls for covariates that do not change over the study period.\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EFor each outcome we selected the patients within the study cohort with the outcome of interest during the study period and ascertained dates when they started and finished taking statins. To improve adjustment for age we included non-users along with new users during the study period. To estimate relative rate ratios we used conditional Poisson regression and adjusted for age in five year bands. We then determined the relative rate ratios for individual statins during the period of use and the washout period (1-182 days after stopping statins) compared with the baseline periods of non-usage during each person\u2019s observation time. We removed the time period in the 28 days before starting statins and the day on which the first prescription was issued. For these analyses we combined men and women. As the occurrence of an event may alter the probability of subsequent statin use we carried out an additional case series analysis restricted to new statin users and started the observation period at first use.\u003Ca id=\u0022xref-ref-44-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-44\u0022\u003E44\u003C\/a\u003E\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-8\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003ENumber needed to treat or number needed to harm\u003C\/h3\u003E\u003Cp id=\u0022p-19\u0022\u003EWe calculated the number needed to treat (NNT) or number needed to harm (NNH) over five years for patients at high risk of cardiovascular disease based on a QRISK2 score of 20% or more, since this group is eligible for statin treatment. For each outcome we used Kaplan-Meier estimates to calculate the disease-free probability at five years for non-users of statins in those aged 35-74 years. For these calculations we identified a cohort of patients who entered the study on the latest of their registration date and 1 January 2002 and who had not been prescribed statins, or had the outcome of interest by that date. These patients were censored at the earliest date of the diagnosis of interest, first statin prescription, death, deregistration with the practice, last upload of computerised data, or date at end of study. We calculated adjusted hazard ratios for each outcome for all types of statin treatment combined, adjusting for potential confounding variables. We then used these adjusted hazard ratios and the disease-free probability to calculate the NNT or NNH for each outcome according to a published formula.\u003Ca id=\u0022xref-ref-45-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-45\u0022\u003E45\u003C\/a\u003E To enable comparisons and supplement data published elsewhere we also used these values to calculate the number of additional cases per 10\u2009000 patients treated over five years.\u003C\/p\u003E\u003Cp id=\u0022p-20\u0022\u003EFor cardiovascular disease, we used information from a recent meta-analysis of 10 primary prevention trials totalling over 70\u2009000 patients with risk factors for cardiovascular disease but without cardiovascular disease at baseline who were treated with statins or placebo and followed up for a median of 4.1 years.\u003Ca id=\u0022xref-ref-2-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003E2\u003C\/a\u003E The meta-analysis reported that the effects of statins on major coronary events and cerebrovascular events were not significantly different according to age, sex, or diabetes status.\u003Ca id=\u0022xref-ref-2-4\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003E2\u003C\/a\u003E We combined the published results for major coronary events and cerebrovascular events using a random effects model to calculate a summary relative risk for cardiovascular disease in statin users compared with non-users. We only included trials that reported both outcomes, assuming that individual patients did not have both outcomes. The overall odds ratio for cardiovascular events associated with statin use in this meta-analysis was 0.76 (95% confidence interval 0.67 to 0.86), which is similar to that reported elsewhere.\u003Ca id=\u0022xref-ref-3-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-3\u0022\u003E3\u003C\/a\u003E We then combined this value with the cardiovascular disease-free probability at five years to calculate the NNT for cardiovascular disease and the number of cases of cardiovascular disease prevented per 10\u2009000 patients treated.\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section results\u0022 id=\u0022results\u0022\u003E\u003Ch2\u003EResults\u003C\/h2\u003E\u003Cp id=\u0022p-21\u0022\u003EOverall, 557 general practices in England and Wales supplying data to the QResearch database met the inclusion criteria, of which 368 were randomly assigned to the study dataset. In total, 2\u2009121\u2009786 patients were aged 30-84 at study entry, of whom 1\u2009778\u2009770 (83.8%) had not been prescribed statins, 9513 (0.5%) were past users, 107\u2009581 (5.1%) were current users, and 225\u2009922 (10.7%) were new users during the study period. Of the new users, 159\u2009790 (70.7%) had been prescribed simvastatin, 50\u2009328 (22.3%) atorvastatin, 8103 (3.6%) pravastatin, 4497 (1.9%) rosuvastatin, and 3204 (1.4%) fluvastatin.\u003C\/p\u003E\u003Cp id=\u0022p-22\u0022\u003ECompared with non-users of statins, new users tended to be older and were more likely to be men and to have comorbidities such as atrial fibrillation, cardiovascular disease, peripheral vascular disease, treated hypertension, diabetes, and chronic kidney disease (table 1\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-down-link\u0022 href=\u0022#T1\u0022\u003E\u003Cspan\u003E\u21d3\u003C\/span\u003E\u003C\/a\u003E). They were also more likely to have results recorded on computer for liver function tests and creatine kinase concentrations.\u003C\/p\u003E\u003Cdiv class=\u0022table pos-float\u0022 id=\u0022T1\u0022\u003E\u003Cdiv class=\u0022table\u0022\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1\u003C\/span\u003E \u003Cp id=\u0022p-23\u0022 class=\u0022first-child\u0022\u003E\u2002Baseline characteristics of study population of new users and non-users of statins. Values are numbers (percentages) unless stated otherwise \u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli\u003E\u003Ca href=\u0022\/highwire\/markup\/590719\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca href=\u0022##\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/590719\/expansion?postprocessors=highwire_figures%2Chighwire_math\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-25\u0022\u003ETable 2\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-down-link\u0022 href=\u0022#T2\u0022\u003E\u003Cspan\u003E\u21d3\u003C\/span\u003E\u003C\/a\u003E shows the crude incidence of each outcome in men and women separately per 10\u2009000 person years. Overall, there were 1969 incident cases of acute renal failure, 12\u2009199 of venous thromboembolism, 5730 of rheumatoid arthritis, 36\u2009541 of cataract, 3553 of Parkinson\u2019s disease, 8784 of dementia, 18\u2009277 of osteoporotic fracture, 1093 of gastric cancer, 1809 of oesophageal cancer, 4152 of colon cancer, 6001 of lung cancer, 2070 of melanoma, 2996 of renal cancer, 9823 of breast cancer, 7129 of prostate cancer, 15\u2009020 of moderate or serious liver dysfunction, and 1406 of moderate or serious myopathy. Sixty two patients had both acute renal failure and moderate or serious myopathy.\u003C\/p\u003E\u003Cdiv class=\u0022table pos-float\u0022 id=\u0022T2\u0022\u003E\u003Cdiv class=\u0022table\u0022\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2\u003C\/span\u003E \u003Cp id=\u0022p-26\u0022 class=\u0022first-child\u0022\u003E\u2002Crude incidence per 10 000 person years for study outcomes in both men and women\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli\u003E\u003Ca href=\u0022\/highwire\/markup\/590725\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca href=\u0022##\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/590725\/expansion?postprocessors=highwire_figures%2Chighwire_math\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-10\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003ENon-significant and marginal clinical outcomes\u003C\/h3\u003E\u003Cp id=\u0022p-28\u0022\u003EThe associations between statins and Parkinson\u2019s disease, rheumatoid arthritis, venous thromboembolism, dementia, osteoporotic fracture, gastric cancer, lung cancer, melanoma, renal cancer, breast cancer, and prostate cancer were not clinically significant and the overall tests for statins were not statistically significant (at P\u0026lt;0.01) (table 3\u003Ca id=\u0022xref-table-wrap-3-1\u0022 class=\u0022xref-down-link\u0022 href=\u0022#T3\u0022\u003E\u003Cspan\u003E\u21d3\u003C\/span\u003E\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv class=\u0022table pos-float\u0022 id=\u0022T3\u0022\u003E\u003Cdiv class=\u0022table\u0022\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 3\u003C\/span\u003E \u003Cp id=\u0022p-29\u0022 class=\u0022first-child\u0022\u003E\u2002Risk associated with statin type both in men and in women for non-significant and marginal outcomes\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli\u003E\u003Ca href=\u0022\/highwire\/markup\/590731\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca href=\u0022##\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/590731\/expansion?postprocessors=highwire_figures%2Chighwire_math\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-31\u0022\u003EAlthough the association between any statin and colon cancer was not significant in women, a significant effect was present in men (overall P=0.002). The risk of colon cancer was lowest among men prescribed pravastatin (adjusted hazard ratio 0.47, 95% confidence interval 0.28 to 0.86), although there was no evidence of a dose-response relation, and increased among men prescribed rosuvastatin (2.07, 1.29 to 3.21). Time varying analysis showed that the risk was increased after three years of treatment (3.27, 1.69 to 6.32) but returned to normal within a year of stopping treatment.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-11\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003ESignificant clinical outcomes\u003C\/h3\u003E\u003Cp id=\u0022p-32\u0022\u003EOutcomes significantly associated with statin use were myopathy, cataract, acute renal failure, oesophageal cancer, and moderate or serious liver dysfunction (table 4\u003Ca id=\u0022xref-table-wrap-4-1\u0022 class=\u0022xref-down-link\u0022 href=\u0022#T4\u0022\u003E\u003Cspan\u003E\u21d3\u003C\/span\u003E\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv class=\u0022table pos-float\u0022 id=\u0022T4\u0022\u003E\u003Cdiv class=\u0022table\u0022\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 4\u003C\/span\u003E \u003Cp id=\u0022p-33\u0022 class=\u0022first-child\u0022\u003E\u2002Risk of significant outcomes associated with statin type both in men and in women\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli\u003E\u003Ca href=\u0022\/highwire\/markup\/590734\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca href=\u0022##\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/590734\/expansion?postprocessors=highwire_figures%2Chighwire_math\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-12\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EModerate or serious liver dysfunction\u003C\/h4\u003E\u003Cp id=\u0022p-35\u0022\u003EOverall, statins were associated with an increased risk of liver dysfunction in both men and women (table 4). In women there was some indication of differences between the effects of individual statins (overall test P=0.058). The highest risk was associated with fluvastatin (2.53, 1.84 to 3.47), which was significantly higher than that with simvastatin (1.52, 1.38 to 1.66). In men, differences between the effects of individual statins were significant (overall test P=0.0045). The highest risk was associated with fluvastatin (1.97 1.43 to 2.72) and the lowest with pravastatin (1.21, 0.93 to 1.58).\u003C\/p\u003E\u003Cp id=\u0022p-36\u0022\u003EA dose-response effect was evident in women, with an increased risk associated with higher doses compared with lower doses (table 5\u003Ca id=\u0022xref-table-wrap-5-1\u0022 class=\u0022xref-down-link\u0022 href=\u0022#T5\u0022\u003E\u003Cspan\u003E\u21d3\u003C\/span\u003E\u003C\/a\u003E). For example, the adjusted hazard ratio for fluvastatin was 3.08 (2.14 to 4.43) at high dose (\u226520 mg) compared with 1.64 (0.88 to 3.06) at low dose (\u226420 mg). The corresponding values for men were 2.37 (1.66 to 3.38) and 1.20 (0.60 to 2.40). This pattern was similar with the other statins.\u003C\/p\u003E\u003Cdiv class=\u0022table pos-float\u0022 id=\u0022T5\u0022\u003E\u003Cdiv class=\u0022table\u0022\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 5\u003C\/span\u003E \u003Cp id=\u0022p-37\u0022 class=\u0022first-child\u0022\u003E\u2002Risk of significant outcomes associated with type and dose of statin both in men and in women\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli\u003E\u003Ca href=\u0022\/highwire\/markup\/590739\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca href=\u0022##\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/590739\/expansion?postprocessors=highwire_figures%2Chighwire_math\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-39\u0022\u003EThe risk of liver dysfunction was highest within the first year of treatment with any statin: the adjusted hazard ratio for women was 2.38 (2.11 to 2.70) and for men was 2.32 (2.07 to 2.59). The hazard ratio in the 1-3 years after starting treatment for women was 1.39 (1.23 to 1.57) and for men was 1.35 (1.21 to 1.51). After stopping statins the risks returned to normal between one and three years in women and from three years in men. Further details on the analyses of duration are available from the authors.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-13\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EModerate or serious myopathy\u003C\/h4\u003E\u003Cp id=\u0022p-40\u0022\u003EAll statins were associated with an increased risk of myopathy (table 4) apart from fluvastatin in women, where numbers were too small for analysis. The direct comparison test showed no significant difference between the effects of individual statins either in men (P=0.57) or in women (P=0.61).\u003C\/p\u003E\u003Cp id=\u0022p-41\u0022\u003EThe adjusted hazard ratios in table 5 show some evidence of a dose-response in men prescribed atorvastatin and pravastatin: 6.11 (4.79 to 7.80) for low dose (10 mg\/day) atorvastatin compared with 8.18 (5.82 to 11.50) for high dose (\u226520 mg\/day) atorvastatin, and 3.62 (1.49 to 8.78) for low dose (\u226420 mg\/day) pravastatin compared with 5.79 (3.07 to 10.91) for high dose (40 mg\/day) pravastatin. The confidence intervals were, however, wide owing to small numbers in each dose category.\u003C\/p\u003E\u003Cp id=\u0022p-42\u0022\u003EThe time varying analysis showed that the risk was highest within the first year of starting treatment: the adjusted hazard ratio in women was 4.30 (2.98 to 6.21) and in men was 9.96 (7.66 to 12.96). The increase persisted during treatment as well as on stopping treatment. From three years after stopping statins, the adjusted hazard ratio in women was 4.65 (2.32 to 9.28) and in men was 5.86 (2.84 to 12.06).\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-14\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003ECataract\u003C\/h4\u003E\u003Cp id=\u0022p-43\u0022\u003EEach statin was associated with an increased risk of cataract in both men and women, apart from fluvastatin in men, owing to small numbers. The direct comparison test showed no significant difference between the effects of individual statins in men (P=0.32) or in women (P=0.82).\u003C\/p\u003E\u003Cp id=\u0022p-44\u0022\u003EThere was no evidence of a dose-response relation (table 5). The time varying analysis showed the risk was significantly increased within a year of starting statins, persisted during treatment, and returned to normal within the first year after stopping treatment.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-15\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EOesophageal cancer\u003C\/h4\u003E\u003Cp id=\u0022p-45\u0022\u003EThe risk of oesophageal cancer decreased in both men and women prescribed simvastatin (0.69, 0.50 to 0.94 and 0.82, 0.68 to 0.99, respectively). The risk was also significantly decreased in men prescribed atorvastatin (0.73, 0.55 to 0.96). The hazard ratios for the other statins were of similar magnitude and all less than 1, but they did not reach statistical significance possibly because of small numbers. The direct comparison test showed no significant difference between the effects of individual statins in either men (P=0.76) or women (P=0.99).\u003C\/p\u003E\u003Cp id=\u0022p-46\u0022\u003EThere was some evidence of a dose-response associated with simvastatin in men only: adjusted hazard ratio 0.91 (0.73 to 1.12) for low dose simvastatin (10\/20 mg) and 0.66 (0.48 to 0.91) for high dose (40\/80 mg) simvastatin (table 5).\u003C\/p\u003E\u003Cp id=\u0022p-47\u0022\u003EThe time varying analysis showed that the reduction in risk of oesophageal cancer was apparent one to three years after starting statins and persisted during the first five years of treatment. In women the risk returned to normal within the first year after stopping treatment and in men one to three years after stopping treatment.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-16\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EAcute renal failure\u003C\/h4\u003E\u003Cp id=\u0022p-48\u0022\u003EThe risk of acute renal failure was increased in both men and women prescribed simvastatin, atorvastatin, and pravastatin (table 4) and in women prescribed fluvastatin. The magnitudes of the adjusted hazard ratios were similar for each statin, ranging from 1.50 to 2.19, and direct comparisons showed no difference in risk by type of statin (P=0.91 in men, P=0.37 in women). Too few patients were prescribed rosuvastatin to draw firm conclusions.\u003C\/p\u003E\u003Cp id=\u0022p-49\u0022\u003EEvidence suggested a dose-response effect (table 5). For example, for women prescribed simvastatin 10\/20 mg the adjusted hazard ratio was 1.38 (1.10 to 1.74) and for simvastatin 40\/80 mg was 1.75 (1.32 to 2.32). For men the corresponding values were 1.39 (1.14 to 1.70) and 2.02 (1.63 to 2.52).\u003C\/p\u003E\u003Cp id=\u0022p-50\u0022\u003EThe increased risk of acute renal failure was apparent within the first year of starting treatment (adjusted hazard ratios 1.54 (1.09 to 2.17) for women and 1.67 (1.26 to 2.21) for men), and persisted for the first five years of treatment. The risk remained increased during the first year of stopping treatment and then returned to normal 1-3 years after stopping treatment: adjusted hazard ratios 1.23 (0.69 to 2.20) for women and 1.57 (0.95 to 2.60) for men.\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-17\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003ECase series analysis\u003C\/h3\u003E\u003Cp id=\u0022p-51\u0022\u003EAs in the cohort analysis the case series analysis for moderate or serious myopathy showed increased risks during statin use compared with no use, although the magnitude of incidence rate ratios was larger than that in the cohort analysis but also had wide confidence intervals (table 6\u003Ca id=\u0022xref-table-wrap-6-1\u0022 class=\u0022xref-down-link\u0022 href=\u0022#T6\u0022\u003E\u003Cspan\u003E\u21d3\u003C\/span\u003E\u003C\/a\u003E). The incidence rate ratios tended to be smaller but still significant when the case series analysis was restricted to new users and the observation period started at first use\u2014for example, the rate ratio for simvastatin was 8.59 (95% confidence interval 5.2 to 14.19) and for atorvastatin was 4.37 (2.27 to 8.44). The rate ratio for pravastatin was higher (33.89, 3.87 to 297.14). Data for fluvastatin and rosuvastatin were insufficient for this analysis.\u003C\/p\u003E\u003Cdiv class=\u0022table pos-float\u0022 id=\u0022T6\u0022\u003E\u003Cdiv class=\u0022table\u0022\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 6\u003C\/span\u003E \u003Cp id=\u0022p-52\u0022 class=\u0022first-child\u0022\u003E\u2002Relative incidence rate ratios from case series analysis for men and women combined for significant outcomes associated with statin type\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli\u003E\u003Ca href=\u0022\/highwire\/markup\/590746\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca href=\u0022##\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/590746\/expansion?postprocessors=highwire_figures%2Chighwire_math\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-54\u0022\u003EThe case series analysis confirmed the significantly increased risk of cataract during the period of use of each statin compared with the period of non-use, except for pravastatin: adjusted incidence rate ratio 1.13 (95% confidence interval 0.92 to 1.40). The risk of acute renal failure was increased during simvastatin use (1.57, 1.27 to 1.95) and also rosuvastatin use (5.11, 1.05 to 24.92) compared with non-use. The increased risk of moderate or serious liver dysfunction during statin use compared with the period of non-use showed a similar pattern and magnitude to the cohort analyses.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-18\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003ENumbers needed to treat and numbers needed to harm\u003C\/h3\u003E\u003Cp id=\u0022p-55\u0022\u003ETable 7\u003Ca id=\u0022xref-table-wrap-7-1\u0022 class=\u0022xref-down-link\u0022 href=\u0022#T7\u0022\u003E\u003Cspan\u003E\u21d3\u003C\/span\u003E\u003C\/a\u003E shows the NNTs and NNHs for each outcome among patients aged 35-74 who were at high risk of cardiovascular disease, as defined by two thresholds (\u226520% and \u226515%) for cardiovascular risk based on the QRISK2 10 year cardiovascular risk score.\u003C\/p\u003E\u003Cdiv class=\u0022table pos-float\u0022 id=\u0022T7\u0022\u003E\u003Cdiv class=\u0022table\u0022\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 7\u003C\/span\u003E \u003Cp id=\u0022p-56\u0022 class=\u0022first-child\u0022\u003E\u2002Numbers needed to harm (NNH) or numbers needed to treat (NNT) and numbers of extra or prevented cases for each outcome over five years in patients aged 35-74 free of cardiovascular disease at baseline with QRISK2 score of \u226520% or \u226515%\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli\u003E\u003Ca href=\u0022\/highwire\/markup\/590750\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca href=\u0022##\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/590750\/expansion?postprocessors=highwire_figures%2Chighwire_math\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-60\u0022\u003EUsing the 20% threshold in women, the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 (95% confidence interval 27 to 64) and for oesophageal cancer was 1266 (850 to 3460). For men, the corresponding values were 33 (24 to 57) and 1082 (711 to 2807).\u003C\/p\u003E\u003Cp id=\u0022p-61\u0022\u003EIn women, the NNH for an additional case of acute renal failure over five years was 434 (284 to 783), for moderate or severe myopathy was 259 (186 to 375), for moderate or severe liver dysfunction was 136 (109 to 175), and for cataract was 33 (28 to 38).\u003C\/p\u003E\u003Cp id=\u0022p-62\u0022\u003EOverall, using the 20% threshold, the NNH or NNTs for men were similar to those for women except for myopathy where the NNH was 91 (74 to 112). This is lower than in women, mainly due to the higher hazard ratio in men.\u003C\/p\u003E\u003Cp id=\u0022p-63\u0022\u003ETable 7 also shows the NNH or NNT for men and women selected using the 15% threshold for QRISK2 score. The event rates for each outcome in non-users of statins tended to be lower than when using the 20% threshold. The effect of this was to increase both the NNT and the NNH for each outcome. Table 7 also shows the estimated numbers of extra cases or cases prevented per 10\u2009000 people treated with statins at both thresholds. For example, using the 20% threshold there would be 271 fewer cases (95% confidence interval 157 to 374) of cardiovascular disease for every 10\u2009000 women compared with 228 fewer cases (132 to 315) using the 15% threshold.\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section discussion\u0022 id=\u0022discussion\u0022\u003E\u003Ch2\u003EDiscussion\u003C\/h2\u003E\u003Cp id=\u0022p-64\u0022\u003EWe examined and quantified the unintended risks and benefits of statins in a large representative primary care population over a six year period. Our study has good face validity because it was carried out in a setting where most patients in the United Kingdom are assessed, treated, and followed up. We were unable to confirm some potential unintended effects of statins, such as a protective effect on risk of Parkinson\u2019s disease, venous thromboembolism,\u003Ca id=\u0022xref-ref-18-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-18\u0022\u003E18\u003C\/a\u003E rheumatoid arthritis,\u003Ca id=\u0022xref-ref-19-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-19\u0022\u003E19\u003C\/a\u003E osteoporotic fracture,\u003Ca id=\u0022xref-ref-25-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-25\u0022\u003E25\u003C\/a\u003E \u003Ca id=\u0022xref-ref-46-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-46\u0022\u003E46\u003C\/a\u003E and dementia.\u003Ca id=\u0022xref-ref-15-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-15\u0022\u003E15\u003C\/a\u003E \u003Ca id=\u0022xref-ref-16-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-16\u0022\u003E16\u003C\/a\u003E This may be because compared with most previous studies our study was larger, prospective, and included more potential confounders.\u003C\/p\u003E\u003Cp id=\u0022p-65\u0022\u003EOur findings largely confirm other studies that reported no clear association between statins and risk of cancers.\u003Ca id=\u0022xref-ref-9-6\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-9\u0022\u003E9\u003C\/a\u003E \u003Ca id=\u0022xref-ref-21-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-21\u0022\u003E21\u003C\/a\u003E \u003Ca id=\u0022xref-ref-23-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-23\u0022\u003E23\u003C\/a\u003E \u003Ca id=\u0022xref-ref-47-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-47\u0022\u003E47\u003C\/a\u003E \u003Ca id=\u0022xref-ref-48-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-48\u0022\u003E48\u003C\/a\u003E There were two potential exceptions: oesophageal cancer, where we found a decreased risk, and colon cancer where there was an apparent decreased risk in men prescribed pravastatin and an increased risk in men prescribed rosuvastatin. These findings could represent a genuine association or could be due to chance, given the large number of outcomes under consideration in this study. Previous studies have not distinguished between the type of statin and specific cancer to this degree\u003Ca id=\u0022xref-ref-9-7\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-9\u0022\u003E9\u003C\/a\u003E \u003Ca id=\u0022xref-ref-21-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-21\u0022\u003E21\u003C\/a\u003E \u003Ca id=\u0022xref-ref-23-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-23\u0022\u003E23\u003C\/a\u003E or undertaken individual patient level analyses. Some of the older meta-analyses did not include rosuvastatin, which has been licensed relatively recently. Further studies using independent datasets should be undertaken to confirm or refute these findings, particularly as the use of statins is likely to increase.\u003C\/p\u003E\u003Cp id=\u0022p-66\u0022\u003EWe were able to quantify adverse effects associated with statins, including myopathy, liver dysfunction, acute renal failure, and cataract. These seem to be class effects, with a dose-response effect apparent for acute renal failure and liver dysfunction consistent with that reported elsewhere.\u003Ca id=\u0022xref-ref-9-8\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-9\u0022\u003E9\u003C\/a\u003E \u003Ca id=\u0022xref-ref-28-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-28\u0022\u003E28\u003C\/a\u003E We found a suggestion of a dose-response for myopathy among men prescribed pravastatin and atorvastatin, although the confidence intervals were wide owing to small numbers. As in previous studies, we found that adverse effects tended to be similar across the types of statins for most outcomes except for liver dysfunction, where the highest risks were associated with fluvastatin. All risks persisted during treatment and were highest in the first year of treatment. After stopping treatment the risk of cataract returned to normal within a year in men and women. Risk of oesophageal cancer returned to normal within a year in women and within 1-3 years in men. Risk of acute renal failure returned to normal within 1-3 years in men and women, and liver dysfunction within 1-3 years in women and from three years in men.\u003C\/p\u003E\u003Cdiv id=\u0022sec-20\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003EComparison with other studies\u003C\/h3\u003E\u003Cp id=\u0022p-67\u0022\u003EClinical trials and their associated meta-analyses provide valuable information on the effectiveness and efficacy of drugs. They are, however, limited in providing information on adverse events since such data are not always recorded or reported in a consistent fashion. Trials tend to be of short duration, under-powered for the detection of adverse events, and susceptible to selection bias, with participants tending to be predominantly white, younger, and healthier than the general population. Most statin trials and meta-analyses are designed to investigate the effectiveness of statins compared with placebo.\u003Ca id=\u0022xref-ref-2-5\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003E2\u003C\/a\u003E Few are specifically designed to investigate adverse events.\u003Ca id=\u0022xref-ref-5-3\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-5\u0022\u003E5\u003C\/a\u003E\u003C\/p\u003E\u003Cp id=\u0022p-68\u0022\u003EOne systematic overview of 35 randomised trials quantified the musculoskeletal, renal, and hepatic effects associated with statin use. This study of 74\u2009102 predominantly white patients, with a mean follow up of 17 months, reported a small excess risk of increases in transaminase concentrations but no increase in risk of myalgias, increased creatine kinase concentrations, or rhabdomyolysis from statin use compared with placebo.\u003Ca id=\u0022xref-ref-8-4\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-8\u0022\u003E8\u003C\/a\u003E The researchers concluded that further study is necessary to determine how their results compare with what occurs in routine practice, particularly among patients who are older, have more severe comorbid conditions, or receive higher statin doses than most patients in these clinical trials.\u003Ca id=\u0022xref-ref-8-5\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-8\u0022\u003E8\u003C\/a\u003E\u003C\/p\u003E\u003Cp id=\u0022p-69\u0022\u003ECholesterol Treatment Trialist Collaborators similarly reported another large meta-analysis of statin trials and reported no increased risk of cancer and a low excess risk of rhabdomyolysis, with a 0.01% excess risk over five years.\u003Ca id=\u0022xref-ref-3-4\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-3\u0022\u003E3\u003C\/a\u003E They did not include liver dysfunction among the adverse outcomes, and other studies where this outcome has been reported have tended to be small.\u003Ca id=\u0022xref-ref-49-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-49\u0022\u003E49\u003C\/a\u003E\u003C\/p\u003E\u003Cp id=\u0022p-70\u0022\u003EOne observational study examined the comparative safety of individual statins for selected outcomes, including myopathy, acute renal failure, and acute liver injury. This study used the general practice research database and involved 100\u2009000 statin users followed for under three years.\u003Ca id=\u0022xref-ref-50-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-50\u0022\u003E50\u003C\/a\u003E Our study adds to this trial by examining a larger population of statin users as well as including non-users, additional outcomes, and a longer duration of follow up. There are two main differences between our study and the general practice research database study. Firstly, we compared new users of statins with non-users whereas the general practice research database study was designed to compare different types of statins directly and did not include a non-user group. Secondly, we used more inclusive outcome definitions and identified many more cases. In the general practice research database study, in order for patients to be included as cases they needed both a computer recorded code of the outcome (for example, acute renal failure) and a computer code indicating admission to hospital, and if only one criterion was met the patient was not identified as a case. In our study we assumed that most patients with, for example, acute renal failure would be admitted to hospital and that the general practitioner would record the diagnostic code rather than the hospital admission itself.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-21\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003EMethodological considerations\u003C\/h3\u003E\u003Cp id=\u0022p-71\u0022\u003EObservational studies, with their large representative and ethnically diverse populations and their potential for longer term follow-up, have limitations, notably bias and unmeasured confounding. Recall bias is not of concern here because information on statin use was prospectively recorded on computer before the outcomes. Misclassification bias of use\u2014that is, statin prescriptions\u2014is possible because low dose simvastatin became available over the counter in August 2004. However, it is likely that most prescriptions are issued in primary care and recorded electronically, especially among elderly people and those with comorbidities, who will have free prescriptions. Any misclassification of statin use (or outcome) if non-differential, would tend to bias the hazard ratios towards 1 thus under-estimating a potential association. Misclassification of outcome is possible, although validation studies undertaken on similar general practice databases relating to similar outcomes where the general practitioner has been contacted for further detail have shown good results.\u003Ca id=\u0022xref-ref-19-4\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-19\u0022\u003E19\u003C\/a\u003E \u003Ca id=\u0022xref-ref-50-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-50\u0022\u003E50\u003C\/a\u003E\u003C\/p\u003E\u003Cp id=\u0022p-72\u0022\u003EAscertainment bias could occur as people starting statins tend to have more blood tests than those not starting statins thereby increasing the likelihood of detection of abnormal liver function tests or myopathy associated with a raised creatine kinase concentration. None the less, our study confirms the results of other studies that statins are associated with liver dysfunction\u003Ca id=\u0022xref-ref-8-6\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-8\u0022\u003E8\u003C\/a\u003E \u003Ca id=\u0022xref-ref-17-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-17\u0022\u003E17\u003C\/a\u003E and gives information on the likely volumes of affected people who need careful follow up. This not only has planning implications for general practitioner workload but may cause anxiety for patients. Our analysis, however, suggests that the risk of abnormal liver function tests is dose dependent and that it can be reversed on stopping treatment, both of which could help guide therapy and reassure people. Ascertainment or recording bias might also partly account for the increased risk of cataract because people prescribed statins may consult their general practitioner more often than the general population thereby increasing the opportunity for people to report on visual problems and be examined.\u003Ca id=\u0022xref-ref-51-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-51\u0022\u003E51\u003C\/a\u003E\u003C\/p\u003E\u003Cp id=\u0022p-73\u0022\u003EIndication bias is particularly important for intended outcomes such as the reduction in risk of cardiovascular disease. Initially, we carried out an additional preliminary analysis using the prior event rate ratios approach\u003Ca id=\u0022xref-ref-52-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-52\u0022\u003E52\u003C\/a\u003E and obtained similar point estimates to those from the published meta-analyses. However, the prior event rate ratios approach is not valid for analyses of first events and cannot be applied if a diagnosis of an outcome before starting study drugs was an exclusion criterion.\u003Ca id=\u0022xref-ref-52-2\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-52\u0022\u003E52\u003C\/a\u003E We have therefore used odds ratios\u003Ca id=\u0022xref-ref-2-6\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-2\u0022\u003E2\u003C\/a\u003E derived from meta-analyses to work out the numbers needed to treat at population level for cardiovascular disease, combined with event rates from QResearch.\u003C\/p\u003E\u003Cp id=\u0022p-74\u0022\u003EOur case series analysis generally confirms the results of our main cohort analyses. It removes the effects of fixed cofounders and largely removes the effect of indication bias, although it could still be susceptible to ascertainment bias.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-22\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003EClinical implications\u003C\/h3\u003E\u003Cp id=\u0022p-75\u0022\u003EAt national level, our study is likely to be useful for policy and planning purposes because we have given the expected numbers of additional adverse events per 10\u2009000 patients that would occur if all patients likely to be at high risk of cardiovascular disease were prescribed statins, assuming the associations we found are causal. We undertook our analyses for NNHs and NNTs at two thresholds of cardiovascular risk (\u226515% and \u226520%) and showed that the potential benefits and harms both tend to increase as the threshold for intervention increases.\u003C\/p\u003E\u003Cp id=\u0022p-76\u0022\u003EOur study may also be useful for informing guidelines on the type and dose of statins. Although adverse outcomes tended to be class effects overall with no significant differences between the statins, the risk of liver dysfunction was highest with fluvastatin. The risk of liver dysfunction, acute renal failure, and possibly myopathy were dose related and, as liver dysfunction is common and the other two outcomes potentially life threatening, the findings would tend to support a policy of using lower doses of statins in people at high risk of the adverse event.\u003C\/p\u003E\u003Cp id=\u0022p-77\u0022\u003EWhile we have shown adverse associations between statin use and four outcomes and one protective association, our study was not designed to show causality. Although we have shown some evidence of dose-response relations and reversibility (in that risk for most outcomes decreases on stopping treatment), consideration of potential biological mechanisms is outside the scope of this study.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-23\u0022 class=\u0022subsection\u0022\u003E\u003Ch3\u003EConclusions\u003C\/h3\u003E\u003Cp id=\u0022p-78\u0022\u003EIn summary, we have reported a detailed epidemiological analysis of the unintended effects of statins in a large representative primary care population for a range of outcomes by type of statin, dose, and duration of use. We have given estimates on the number of additional events potentially caused or prevented per 10\u2009000 patients treated. The current paper quantifies risks and benefits of statins at population level, but the underlying algorithms also can be applied at the individual level. In a companion paper,\u003Ca id=\u0022xref-ref-53-1\u0022 class=\u0022xref-bibr\u0022 href=\u0022#ref-53\u0022\u003E53\u003C\/a\u003E therefore, we validate the algorithms at individual level so that they can be used to explain absolute and relative risks and benefits for an individual patient as well as to identify those at high risk of adverse events from statins for more proactive monitoring.\u003C\/p\u003E\u003Cdiv class=\u0022style3\u0022 id=\u0022boxed-text-1\u0022\u003E\u003Cdiv id=\u0022sec-24\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EWhat is already known on this topic\u003C\/h4\u003E\u003Cul class=\u0022list-simple\u0022 id=\u0022list-1\u0022\u003E\u003Cli id=\u0022list-item-1\u0022\u003E\u003Cp id=\u0022p-79\u0022\u003EMeta-analyses suggest that statins reduce the risk of cardiovascular disease, particularly in high risk patients\u003C\/p\u003E\u003C\/li\u003E\u003Cli id=\u0022list-item-2\u0022\u003E\u003Cp id=\u0022p-80\u0022\u003EAlthough meta-analyses provide valuable information on effectiveness they tend to lack representative samples, duration of follow-up, or power to assess unintended effects\u003C\/p\u003E\u003C\/li\u003E\u003Cli id=\u0022list-item-3\u0022\u003E\u003Cp id=\u0022p-81\u0022\u003EInformation on the unintended effects of statins in representative primary care populations is lacking although statins are prescribed in large volumes for long periods\u003C\/p\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv id=\u0022sec-25\u0022 class=\u0022subsection\u0022\u003E\u003Ch4\u003EWhat this study adds\u003C\/h4\u003E\u003Cul class=\u0022list-simple\u0022 id=\u0022list-2\u0022\u003E\u003Cli id=\u0022list-item-4\u0022\u003E\u003Cp id=\u0022p-82\u0022\u003EIndividual statins were not significantly associated with risk of Parkinson\u2019s disease, rheumatoid arthritis, venous thromboembolism, dementia, osteoporotic fracture, and several common cancers\u003C\/p\u003E\u003C\/li\u003E\u003Cli id=\u0022list-item-5\u0022\u003E\u003Cp id=\u0022p-83\u0022\u003EThe risk of oesophageal cancer was reduced but for liver dysfunction, acute renal failure, myopathy, and cataract it was increased\u003C\/p\u003E\u003C\/li\u003E\u003Cli id=\u0022list-item-6\u0022\u003E\u003Cp id=\u0022p-84\u0022\u003EAdverse effects were similar across the statin types for each outcome except liver dysfunction where fluvastatin was associated with the highest risks\u003C\/p\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section notes\u0022 id=\u0022notes-2\u0022\u003E\u003Ch2\u003ENotes\u003C\/h2\u003E\u003Cp id=\u0022p-91\u0022\u003E\u003Cstrong\u003ECite this as:\u003C\/strong\u003E \u003Cem\u003EBMJ\u003C\/em\u003E 2010;340:c2197\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section fn-group\u0022 id=\u0022fn-group-1\u0022\u003E\u003Ch2\u003EFootnotes\u003C\/h2\u003E\u003Cul\u003E\u003Cli class=\u0022fn\u0022 id=\u0022fn-1\u0022\u003E\u003Cp id=\u0022p-85\u0022\u003EWe thank the contribution of practices using the Egton Medical Information System (EMIS) who provide data to QResearch and to David Stables (medical director, EMIS) for his expertise in establishing, developing, and supporting the database and to ClinRisk who undertook the study .\u003C\/p\u003E\u003C\/li\u003E\u003Cli class=\u0022fn-participating-researchers\u0022 id=\u0022fn-2\u0022\u003E\u003Cp id=\u0022p-86\u0022\u003EContributors: JH-C initiated the study, reviewed the literature, extracted and manipulated the data, carried out the primary data analysis, and wrote the first draft of the paper. CC contributed to the design, analysis, interpretation, and drafting of the paper. Both authors are guarantors.\u003C\/p\u003E\u003C\/li\u003E\u003Cli class=\u0022fn-financial-disclosure\u0022 id=\u0022fn-3\u0022\u003E\u003Cp id=\u0022p-87\u0022\u003EFunding: No external funding.\u003C\/p\u003E\u003C\/li\u003E\u003Cli class=\u0022fn-conflict\u0022 id=\u0022fn-4\u0022\u003E\u003Cp id=\u0022p-88\u0022\u003ECompeting interests: JH-C is codirector of QResearch (a not for profit organisation that is a joint partnership between the University of Nottingham and EMIS, the leading commercial supplier of IT for 60% of general practices in the United Kingdom) and director of ClinRisk, which produces software to ensure the reliable and updatable implementation of clinical risk algorithms within clinical computer systems to improve patient care. CC is a consultant statistician for ClinRisk. This work and any views expressed within it are solely those of the authors and not of any affiliated bodies or organisations.\u003C\/p\u003E\u003C\/li\u003E\u003Cli class=\u0022fn\u0022 id=\u0022fn-5\u0022\u003E\u003Cp id=\u0022p-89\u0022\u003EEthical approval: This study was independently reviewed in accordance with the QResearch agreement with Trent research ethics committee.\u003C\/p\u003E\u003C\/li\u003E\u003Cli class=\u0022fn\u0022 id=\u0022fn-6\u0022\u003E\u003Cp id=\u0022p-90\u0022\u003EData sharing: The patient level data from the QResearch are specifically licensed according to its governance framework. See \u003Ca href=\u0022http:\/\/www.qresearch.org\u0022\u003Ewww.qresearch.org\u003C\/a\u003E for further details. The Read codes groups used are available from the authors on request.\u003C\/p\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022license\u0022 id=\u0022license-1\u0022\u003E\u003Cp id=\u0022p-1\u0022\u003EThis is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: \u003Ca href=\u0022http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/\u0022\u003Ehttp:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/\u003C\/a\u003E and \u003Ca href=\u0022http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/legalcode\u0022\u003Ehttp:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/legalcode\u003C\/a\u003E.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section ref-list\u0022 id=\u0022ref-list-1\u0022\u003E\u003Ch2\u003EReferences\u003C\/h2\u003E\u003Col class=\u0022cit-list\u0022\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-1-1\u0022 title=\u0022View reference 1 in text\u0022 id=\u0022ref-1\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-340.may19_4.c2197.1\u0022\u003E\u003Cdiv class=\u0022cit-metadata unstructured\u0022\u003EBritish Heart Foundation. Coronary heart disease statistics. 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The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EBMJ\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2009\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E338\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003Eb2376\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DBMJ%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.b2376%26rft_id%253Dinfo%253Apmid%252F19567909%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjE3OiIzMzgvanVuMzBfMS9iMjM3NiI7czo0OiJhdG9tIjtzOjIzOiIvYm1qLzM0MC9ibWouYzIxOTcuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-3-1\u0022 title=\u0022View reference 3 in text\u0022 id=\u0022ref-3\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.3\u0022 data-doi=\u002210.1016\/S0140-6736(05)67394-1\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ECholesterol Treatment Trialist Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003ELancet\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2005\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E366\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1267\u003C\/span\u003E-78.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DBaigent%26rft.auinit1%253DC.%26rft.volume%253D366%26rft.issue%253D9493%26rft.spage%253D1267%26rft.epage%253D1278%26rft.atitle%253DEfficacy%2Band%2Bsafety%2Bof%2Bcholesterol-lowering%2Btreatment%253A%2Bprospective%2Bmeta-analysis%2Bof%2Bdata%2Bfrom%2B90%252C056%2Bparticipants%2Bin%2B14%2Brandomised%2Btrials%2Bof%2Bstatins.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252805%252967394-1%26rft_id%253Dinfo%253Apmid%252F16214597%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1016\/S0140-6736(05)67394-1\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=16214597\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000232405700025\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-4-1\u0022 title=\u0022View reference 4 in text\u0022 id=\u0022ref-4\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-340.may19_4.c2197.4\u0022\u003E\u003Cdiv class=\u0022cit-metadata unstructured\u0022\u003EDepartment of Health. 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Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EArch Intern Med\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2006\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E166\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E2307\u003C\/span\u003E-13.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DArchives%2Bof%2BInternal%2BMedicine%26rft.stitle%253DArch%2BIntern%2BMed%26rft.issn%253D0003-9926%26rft.aulast%253DThavendiranathan%26rft.auinit1%253DP.%26rft.volume%253D166%26rft.issue%253D21%26rft.spage%253D2307%26rft.epage%253D2313%26rft.atitle%253DPrimary%2BPrevention%2Bof%2BCardiovascular%2BDiseases%2BWith%2BStatin%2BTherapy%253A%2BA%2BMeta-analysis%2Bof%2BRandomized%2BControlled%2BTrials%26rft_id%253Dinfo%253Adoi%252F10.1001%252Farchinte.166.21.2307%26rft_id%253Dinfo%253Apmid%252F17130382%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/archinte.166.21.2307\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=17130382\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000242312700002\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-6-1\u0022 title=\u0022View reference 6 in text\u0022 id=\u0022ref-6\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-340.may19_4.c2197.6\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EHippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R, Sheikh A, et al. 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QRISK or Framingham for predicting cardiovascular risk? \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EBMJ\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2009\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E339\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003Eb2673\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DBMJ%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.b2673%26rft_id%253Dinfo%253Apmid%252F19584410%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjE3OiIzMzkvanVsMDdfMi9iMjY3MyI7czo0OiJhdG9tIjtzOjIzOiIvYm1qLzM0MC9ibWouYzIxOTcuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-8-1\u0022 title=\u0022View reference 8 in text\u0022 id=\u0022ref-8\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.8\u0022 data-doi=\u002210.1161\/CIRCULATIONAHA.106.624890\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EKashani A, Phillips CO, Foody JM, Wang Y, Mangalmurti S, Ko DT, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003ECirculation\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2006\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E114\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E2788\u003C\/span\u003E-97.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DCirculation%26rft_id%253Dinfo%253Adoi%252F10.1161%252FCIRCULATIONAHA.106.624890%26rft_id%253Dinfo%253Apmid%252F17159064%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTQ6ImNpcmN1bGF0aW9uYWhhIjtzOjU6InJlc2lkIjtzOjExOiIxMTQvMjUvMjc4OCI7czo0OiJhdG9tIjtzOjIzOiIvYm1qLzM0MC9ibWouYzIxOTcuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-9-1\u0022 title=\u0022View reference 9 in text\u0022 id=\u0022ref-9\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.9\u0022 data-doi=\u002210.1016\/j.jacc.2007.02.073\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EAlsheikh-Ali AA, Maddukuri PV, Han H, Karas RH. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJ Am Coll Cardiol\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2007\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E50\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E409\u003C\/span\u003E-18.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJ%2BAm%2BColl%2BCardiol%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.jacc.2007.02.073%26rft_id%253Dinfo%253Apmid%252F17662392%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1016\/j.jacc.2007.02.073\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=17662392\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000248515600004\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-10-1\u0022 title=\u0022View reference 10 in text\u0022 id=\u0022ref-10\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.10\u0022 data-doi=\u002210.1016\/j.clinthera.2007.08.022\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ENichols G, Koro G. Does statin therapy initiation increase the risk for myopathy? An observational study of 32,225 diabetic and non diabetic patients. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EClin Therap\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2007\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E29\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1761\u003C\/span\u003E-70.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DClinical%2Btherapeutics%26rft.stitle%253DClin%2BTher%26rft.aulast%253DNichols%26rft.auinit1%253DG.%2BA.%26rft.volume%253D29%26rft.issue%253D8%26rft.spage%253D1761%26rft.epage%253D1770%26rft.atitle%253DDoes%2Bstatin%2Btherapy%2Binitiation%2Bincrease%2Bthe%2Brisk%2Bfor%2Bmyopathy%253F%2BAn%2Bobservational%2Bstudy%2Bof%2B32%252C225%2Bdiabetic%2Band%2Bnondiabetic%2Bpatients.%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.clinthera.2007.08.022%26rft_id%253Dinfo%253Apmid%252F17919557%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1016\/j.clinthera.2007.08.022\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=17919557\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000249682900022\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-11-1\u0022 title=\u0022View reference 11 in text\u0022 id=\u0022ref-11\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.11\u0022 data-doi=\u002210.1016\/j.jclinepi.2004.10.004\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EAndrade SE, Graham DJ, Staffa JA, Schech SD, Shatin D, La Grenade L, et al. Health plan administrative databases can efficiently identify serious myopathy and rhabdomyolysis. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJ Clin Epidemiol\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2005\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E58\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E171\u003C\/span\u003E-4.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJournal%2Bof%2Bclinical%2Bepidemiology%26rft.stitle%253DJ%2BClin%2BEpidemiol%26rft.aulast%253DAndrade%26rft.auinit1%253DS.%2BE.%26rft.volume%253D58%26rft.issue%253D2%26rft.spage%253D171%26rft.epage%253D174%26rft.atitle%253DHealth%2Bplan%2Badministrative%2Bdatabases%2Bcan%2Befficiently%2Bidentify%2Bserious%2Bmyopathy%2Band%2Brhabdomyolysis.%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.jclinepi.2004.10.004%26rft_id%253Dinfo%253Apmid%252F15680751%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1016\/j.jclinepi.2004.10.004\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=15680751\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000227083600012\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-12-1\u0022 title=\u0022View reference 12 in text\u0022 id=\u0022ref-12\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.12\u0022 data-doi=\u002210.1001\/jama.292.21.2585\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EGraham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJAMA\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2004\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E292\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E2585\u003C\/span\u003E-90.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJAMA%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.292.21.2585%26rft_id%253Dinfo%253Apmid%252F15572716%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/jama.292.21.2585\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=15572716\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000225409100021\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-13-1\u0022 title=\u0022View reference 13 in text\u0022 id=\u0022ref-13\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.13\u0022 data-doi=\u002210.1001\/jama.289.13.1681\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EThompson PD, Clarkson P, Karas RH. Statin-associated myopathy. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJAMA\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2003\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E289\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1681\u003C\/span\u003E-90.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DThompson%26rft.auinit1%253DP.%2BD.%26rft.volume%253D289%26rft.issue%253D13%26rft.spage%253D1681%26rft.epage%253D1690%26rft.atitle%253DStatin-Associated%2BMyopathy%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.289.13.1681%26rft_id%253Dinfo%253Apmid%252F12672737%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/jama.289.13.1681\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=12672737\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000181944500032\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-14-1\u0022 title=\u0022View reference 14 in text\u0022 id=\u0022ref-14\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.14\u0022 data-doi=\u002210.1002\/mds.21290\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EHuang X, Chen H, Miller W, Mailman RB, Woodard JL, Chen PC, et al. Lower low-density lipoprotein cholesterol levels are associated with Parkinson\u2019s disease. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EMov Disord\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2007\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E22\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E377\u003C\/span\u003E-81.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DMovement%2Bdisorders%2B%253A%2B%2Bofficial%2Bjournal%2Bof%2Bthe%2BMovement%2BDisorder%2BSociety%26rft.stitle%253DMov%2BDisord%26rft.aulast%253DHuang%26rft.auinit1%253DX.%26rft.volume%253D22%26rft.issue%253D3%26rft.spage%253D377%26rft.epage%253D381%26rft.atitle%253DLower%2Blow-density%2Blipoprotein%2Bcholesterol%2Blevels%2Bare%2Bassociated%2Bwith%2BParkinson%2527s%2Bdisease.%26rft_id%253Dinfo%253Adoi%252F10.1002%252Fmds.21290%26rft_id%253Dinfo%253Apmid%252F17177184%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1002\/mds.21290\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=17177184\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000245012700014\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-15-1\u0022 title=\u0022View reference 15 in text\u0022 id=\u0022ref-15\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.15\u0022 data-doi=\u002210.1016\/S0140-6736(00)03155-X\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EJick H, Zornberg G, Jick S, Seshadri S, Drachman D. Statins and risk of dementia. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003ELancet\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2000\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E356\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1627\u003C\/span\u003E-31.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DJick%26rft.auinit1%253DH.%26rft.volume%253D356%26rft.issue%253D9242%26rft.spage%253D1627%26rft.epage%253D1631%26rft.atitle%253DStatins%2Band%2Bthe%2Brisk%2Bof%2Bdementia.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252800%252903155-X%26rft_id%253Dinfo%253Apmid%252F11089820%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1016\/S0140-6736(00)03155-X\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=11089820\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000165249200009\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-16-1\u0022 title=\u0022View reference 16 in text\u0022 id=\u0022ref-16\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.16\u0022 data-doi=\u002210.1212\/01.wnl.0000279333.77404.d7\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ESzwast SJ, Hendrie HC, Lane KA, Gao S, Taylor SE, Unverzagt F, et al. Association of statin use with cognitive decline in elderly African Americans. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003ENeurology\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2007\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E69\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1873\u003C\/span\u003E-80.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DNeurology%26rft.stitle%253DNeurology%26rft.issn%253D0028-3878%26rft.aulast%253DSzwast%26rft.auinit1%253DS.%2BJ.%26rft.volume%253D69%26rft.issue%253D19%26rft.spage%253D1873%26rft.epage%253D1880%26rft.atitle%253DAssociation%2Bof%2Bstatin%2Buse%2Bwith%2Bcognitive%2Bdecline%2Bin%2Belderly%2BAfrican%2BAmericans%26rft_id%253Dinfo%253Adoi%252F10.1212%252F01.wnl.0000279333.77404.d7%26rft_id%253Dinfo%253Apmid%252F17984456%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjEwOiI2OS8xOS8xODczIjtzOjQ6ImF0b20iO3M6MjM6Ii9ibWovMzQwL2Jtai5jMjE5Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-17-1\u0022 title=\u0022View reference 17 in text\u0022 id=\u0022ref-17\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.17\u0022 data-doi=\u002210.1161\/01.CIR.101.2.207\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EMaron DJ, Fazio S, Linton MF. Current perspectives on statins. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003ECirculation\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2000\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E101\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E207\u003C\/span\u003E-13.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DCirculation%26rft.stitle%253DCirculation%26rft.issn%253D0009-7322%26rft.aulast%253DMaron%26rft.auinit1%253DD.%2BJ.%26rft.volume%253D101%26rft.issue%253D2%26rft.spage%253D207%26rft.epage%253D213%26rft.atitle%253DCurrent%2BPerspectives%2Bon%2BStatins%26rft_id%253Dinfo%253Adoi%252F10.1161%252F01.CIR.101.2.207%26rft_id%253Dinfo%253Apmid%252F10637210%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTQ6ImNpcmN1bGF0aW9uYWhhIjtzOjU6InJlc2lkIjtzOjk6IjEwMS8yLzIwNyI7czo0OiJhdG9tIjtzOjIzOiIvYm1qLzM0MC9ibWouYzIxOTcuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-18-1\u0022 title=\u0022View reference 18 in text\u0022 id=\u0022ref-18\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.18\u0022 data-doi=\u002210.1001\/archinte.161.11.1405\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ERay JG, Mamdani M, Tsuyuki RT, Anderson DR, Yeo EL, Laupacis A. Use of statins and the subsequent development of deep vein thrombosis. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EArch Intern Med\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2001\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E161\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1405\u003C\/span\u003E-10.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DArchives%2Bof%2BInternal%2BMedicine%26rft.stitle%253DArch%2BIntern%2BMed%26rft.issn%253D0003-9926%26rft.aulast%253DRay%26rft.auinit1%253DJ.%2BG.%26rft.volume%253D161%26rft.issue%253D11%26rft.spage%253D1405%26rft.epage%253D1410%26rft.atitle%253DUse%2Bof%2BStatins%2Band%2Bthe%2BSubsequent%2BDevelopment%2Bof%2BDeep%2BVein%2BThrombosis%26rft_id%253Dinfo%253Adoi%252F10.1001%252Farchinte.161.11.1405%26rft_id%253Dinfo%253Apmid%252F11386889%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/archinte.161.11.1405\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=11386889\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000169136400005\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-19-1\u0022 title=\u0022View reference 19 in text\u0022 id=\u0022ref-19\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.19\u0022 data-doi=\u002210.1136\/ard.2008.091967\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EJick SS, Choi H, Li L, McInnes IB, Sattar N. Hyperlipidemia, statin use and the risk of developing rheumatoid arthritis. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EAnn Rheum Dis\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2009\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E68\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E546\u003C\/span\u003E-51.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DAnn%2BRheum%2BDis%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fard.2008.091967%26rft_id%253Dinfo%253Apmid%252F18662929%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTE6ImFubnJoZXVtZGlzIjtzOjU6InJlc2lkIjtzOjg6IjY4LzQvNTQ2IjtzOjQ6ImF0b20iO3M6MjM6Ii9ibWovMzQwL2Jtai5jMjE5Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-20-1\u0022 title=\u0022View reference 20 in text\u0022 id=\u0022ref-20\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.20\u0022 data-doi=\u002210.1001\/jama.295.23.2752\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EKlein BEK, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJAMA\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2006\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E295\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E2752\u003C\/span\u003E-8.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DKlein%26rft.auinit1%253DB.%2BE.%2BK.%26rft.volume%253D295%26rft.issue%253D23%26rft.spage%253D2752%26rft.epage%253D2758%26rft.atitle%253DStatin%2BUse%2Band%2BIncident%2BNuclear%2BCataract%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.295.23.2752%26rft_id%253Dinfo%253Apmid%252F16788130%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/jama.295.23.2752\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=16788130\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000238389700030\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-21-1\u0022 title=\u0022View reference 21 in text\u0022 id=\u0022ref-21\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.21\u0022 data-doi=\u002210.1001\/jama.295.1.74\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EDale K, Coleman C, Hentyan N, Kluger J, White C. Statins and cancer risk\u2014a meta-analysis. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJAMA\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2006\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E295\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E74\u003C\/span\u003E-80.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DDale%26rft.auinit1%253DK.%2BM.%26rft.volume%253D295%26rft.issue%253D1%26rft.spage%253D74%26rft.epage%253D80%26rft.atitle%253DStatins%2Band%2BCancer%2BRisk%253A%2BA%2BMeta-analysis%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.295.1.74%26rft_id%253Dinfo%253Apmid%252F16391219%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/jama.295.1.74\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=16391219\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000234381100023\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-22-1\u0022 title=\u0022View reference 22 in text\u0022 id=\u0022ref-22\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.22\u0022 data-doi=\u002210.1006\/bbrc.1996.0494\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EAddeo R, Altucci L, Battista T, Bonapace IM, Cancemi M, Cicatiello L, et al. Stimulation of human breast cancer MCF-7 cells with estrogen prevents cell cycle arrest by HMG-CoA reductase inhibitors. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EBiochem Biophys Res Commun\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E1996\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E220\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E864\u003C\/span\u003E-70.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DBiochemical%2Band%2Bbiophysical%2Bresearch%2Bcommunications%26rft.stitle%253DBiochem%2BBiophys%2BRes%2BCommun%26rft.aulast%253DAddeo%26rft.auinit1%253DR.%26rft.volume%253D220%26rft.issue%253D3%26rft.spage%253D864%26rft.epage%253D870%26rft.atitle%253DStimulation%2Bof%2Bhuman%2Bbreast%2Bcancer%2BMCF-7%2Bcells%2Bwith%2Bestrogen%2Bprevents%2Bcell%2Bcycle%2Barrest%2Bby%2BHMG-CoA%2Breductase%2Binhibitors.%26rft_id%253Dinfo%253Adoi%252F10.1006%252Fbbrc.1996.0494%26rft_id%253Dinfo%253Apmid%252F8607857%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1006\/bbrc.1996.0494\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=8607857\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=A1996UE85300067\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-23-1\u0022 title=\u0022View reference 23 in text\u0022 id=\u0022ref-23\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.23\u0022 data-doi=\u002210.1200\/JCO.2006.06.3560\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EBonovas S, Filioussi K, Tsavaris N, Sitaras NM. Statins and cancer risk: a literature-based meta-analysis and meta-regression analysis of 35 randomized controlled trials. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJ Clin Oncol\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2006\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E24\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E4808\u003C\/span\u003E-17.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJ%2BClin%2BOncol%26rft_id%253Dinfo%253Adoi%252F10.1200%252FJCO.2006.06.3560%26rft_id%253Dinfo%253Apmid%252F17001070%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIyNC8zMC80ODA4IjtzOjQ6ImF0b20iO3M6MjM6Ii9ibWovMzQwL2Jtai5jMjE5Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-24-1\u0022 title=\u0022View reference 24 in text\u0022 id=\u0022ref-24\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.24\u0022 data-doi=\u002210.1001\/jama.1996.03530250059028\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ENewman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJAMA\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E1996\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E275\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E55\u003C\/span\u003E-60.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DNewman%26rft.auinit1%253DT.%2BB.%26rft.volume%253D275%26rft.issue%253D1%26rft.spage%253D55%26rft.epage%253D60%26rft.atitle%253DCarcinogenicity%2Bof%2BLipid-Lowering%2BDrugs%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.1996.03530250059028%26rft_id%253Dinfo%253Apmid%252F8531288%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/jama.1996.03530250059028\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=8531288\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=A1996TM23800023\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-25-1\u0022 title=\u0022View reference 25 in text\u0022 id=\u0022ref-25\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.25\u0022 data-doi=\u002210.1001\/jama.283.24.3205\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EMeier CR, Schlienger RG, Kraenzlin ME, Schlegel B, Jick H. HMG-CoA reductase inhibitors and the risk of fractures. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJAMA\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2000\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E283\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E3205\u003C\/span\u003E-10.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DMeier%26rft.auinit1%253DC.%2BR.%26rft.volume%253D283%26rft.issue%253D24%26rft.spage%253D3205%26rft.epage%253D3210%26rft.atitle%253DHMG-CoA%2BReductase%2BInhibitors%2Band%2Bthe%2BRisk%2Bof%2BFractures%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.283.24.3205%26rft_id%253Dinfo%253Apmid%252F10866867%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/jama.283.24.3205\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10866867\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000087753900032\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-26-1\u0022 title=\u0022View reference 26 in text\u0022 id=\u0022ref-26\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.26\u0022 data-doi=\u002210.7326\/0003-4819-139-2-200307150-00009\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ELaCroix AZ, Cauley JA, Pettinger M, Hsia J, Bauer DC, McGowan J, et al. Statin use, clinical fracture, and bone density in postmenopausal women: results from the Women\u2019s Health Initiative Observational Study. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EAnn Intern Med\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2003\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E139\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E97\u003C\/span\u003E-104.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DAnnals%2Bof%2BInternal%2BMedicine%26rft.stitle%253DANN%2BINTERN%2BMED%26rft.issn%253D0003-4819%26rft.aulast%253DLaCroix%26rft.auinit1%253DA.%2BZ.%26rft.volume%253D139%26rft.issue%253D2%26rft.spage%253D97%26rft.epage%253D104%26rft.atitle%253DStatin%2BUse%252C%2BClinical%2BFracture%252C%2Band%2BBone%2BDensity%2Bin%2BPostmenopausal%2BWomen%253A%2BResults%2Bfrom%2Bthe%2BWomen%2527s%2BHealth%2BInitiative%2BObservational%2BStudy%26rft_id%253Dinfo%253Adoi%252F10.7326%252F0003-4819-139-2-200307150-00009%26rft_id%253Dinfo%253Apmid%252F12859159%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.7326\/0003-4819-139-2-200307150-00009\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=12859159\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000184163100003\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-27-1\u0022 title=\u0022View reference 27 in text\u0022 id=\u0022ref-27\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.27\u0022 data-doi=\u002210.1001\/jama.283.24.3255\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ECummings SR, Bauer DC. Do statins prevent both cardiovascular disease and fracture? \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EJAMA\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2000\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E283\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E3255\u003C\/span\u003E-7.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DCummings%26rft.auinit1%253DS.%2BR.%26rft.volume%253D283%26rft.issue%253D24%26rft.spage%253D3255%26rft.epage%253D3257%26rft.atitle%253DDo%2BStatins%2BPrevent%2BBoth%2BCardiovascular%2BDisease%2Band%2BFracture%253F%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.283.24.3255%26rft_id%253Dinfo%253Apmid%252F10866875%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/jama.283.24.3255\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10866875\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000087753900040\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-28-1\u0022 title=\u0022View reference 28 in text\u0022 id=\u0022ref-28\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.28\u0022 data-doi=\u002210.1016\/S0140-6736(04)16513-6\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EWolfe SM. Dangers of rosuvastatin identified before and after FDA approval. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003ELancet\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2004\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E363\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E2189\u003C\/span\u003E-90.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DWolfe%26rft.auinit1%253DS.%2BM.%26rft.volume%253D363%26rft.issue%253D9427%26rft.spage%253D2189%26rft.epage%253D2190%26rft.atitle%253DDangers%2Bof%2Brosuvastatin%2Bidentified%2Bbefore%2Band%2Bafter%2BFDA%2Bapproval.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252804%252916513-6%26rft_id%253Dinfo%253Apmid%252F15220045%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1016\/S0140-6736(04)16513-6\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=15220045\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000222268300026\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-29-1\u0022 title=\u0022View reference 29 in text\u0022 id=\u0022ref-29\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-other\u0022 id=\u0022cit-340.may19_4.c2197.29\u0022\u003E\u003Cdiv class=\u0022cit-metadata unstructured\u0022\u003EFood and Drug Admininstration. 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The self controlled case series method. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EBMJ\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2008\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E337\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003Ea1069\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DWhitaker%26rft.auinit1%253DH.%26rft.volume%253D337%26rft.issue%253Daug28_2%26rft.spage%253Da1069%26rft.epage%253Da1069%26rft.atitle%253DThe%2Bself%2Bcontrolled%2Bcase%2Bseries%2Bmethod%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.a1069%26rft_id%253Dinfo%253Apmid%252F18755768%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjE3OiIzMzcvYXVnMjhfMi9hMTA2OSI7czo0OiJhdG9tIjtzOjIzOiIvYm1qLzM0MC9ibWouYzIxOTcuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-42-1\u0022 title=\u0022View reference 42 in text\u0022 id=\u0022ref-42\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.42\u0022 data-doi=\u002210.1136\/bmj.a1227\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EDouglas IJ, Smeeth L. Exposure to antipsychotics and risk of stroke: self controlled case series study. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EBMJ\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2008\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E337\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003Ea1227\u003C\/span\u003E.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DDouglas%26rft.auinit1%253DI.%2BJ%26rft.volume%253D337%26rft.issue%253Daug28_2%26rft.spage%253Da1227%26rft.epage%253Da1227%26rft.atitle%253DExposure%2Bto%2Bantipsychotics%2Band%2Brisk%2Bof%2Bstroke%253A%2Bself%2Bcontrolled%2Bcase%2Bseries%2Bstudy%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.a1227%26rft_id%253Dinfo%253Apmid%252F18755769%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjE3OiIzMzcvYXVnMjhfMi9hMTIyNyI7czo0OiJhdG9tIjtzOjIzOiIvYm1qLzM0MC9ibWouYzIxOTcuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-43-1\u0022 title=\u0022View reference 43 in text\u0022 id=\u0022ref-43\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.43\u0022 data-doi=\u002210.1136\/hrt.2004.037457\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ETata LJ, West J, Smith C, Farrington P, Card T, Smeeth L, et al. General population based study of the impact of tricyclic and selective serotonin reuptake inhibitor antidepressants on the risk of acute myocardial infarction. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EHeart\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2005\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E91\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E465\u003C\/span\u003E-71.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DHeart%26rft.stitle%253DHeart%26rft.issn%253D0007-0769%26rft.aulast%253DTata%26rft.auinit1%253DL%2BJ%26rft.volume%253D91%26rft.issue%253D4%26rft.spage%253D465%26rft.epage%253D471%26rft.atitle%253DGeneral%2Bpopulation%2Bbased%2Bstudy%2Bof%2Bthe%2Bimpact%2Bof%2Btricyclic%2Band%2Bselective%2Bserotonin%2Breuptake%2Binhibitor%2Bantidepressants%2Bon%2Bthe%2Brisk%2Bof%2Bacute%2Bmyocardial%2Binfarction%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fhrt.2004.037457%26rft_id%253Dinfo%253Apmid%252F15772201%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiaGVhcnRqbmwiO3M6NToicmVzaWQiO3M6ODoiOTEvNC80NjUiO3M6NDoiYXRvbSI7czoyMzoiL2Jtai8zNDAvYm1qLmMyMTk3LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-44-1\u0022 title=\u0022View reference 44 in text\u0022 id=\u0022ref-44\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.44\u0022 data-doi=\u002210.1002\/sim.2302\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EWhitaker HJ, Farrington CP, Spiessens B, Musonda P. Tutorial in biostatistics: the self-controlled case series method. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EStat Med\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2006\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E25\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1768\u003C\/span\u003E-97.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DStatistics%2Bin%2Bmedicine%26rft.stitle%253DStat%2BMed%26rft.aulast%253DWhitaker%26rft.auinit1%253DH.%2BJ.%26rft.volume%253D25%26rft.issue%253D10%26rft.spage%253D1768%26rft.epage%253D1797%26rft.atitle%253DTutorial%2Bin%2Bbiostatistics%253A%2Bthe%2Bself-controlled%2Bcase%2Bseries%2Bmethod.%26rft_id%253Dinfo%253Adoi%252F10.1002%252Fsim.2302%26rft_id%253Dinfo%253Apmid%252F16220518%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1002\/sim.2302\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=16220518\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000237869100013\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-45-1\u0022 title=\u0022View reference 45 in text\u0022 id=\u0022ref-45\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.45\u0022 data-doi=\u002210.1136\/bmj.319.7223.1492\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EAltman DG, Andersen PK. Calculating the number needed to treat for trials where the outcome is time to an event. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EBMJ\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E1999\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E319\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1492\u003C\/span\u003E-5.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DAltman%26rft.auinit1%253DD.%2BG%26rft.volume%253D319%26rft.issue%253D7223%26rft.spage%253D1492%26rft.epage%253D1495%26rft.atitle%253DCalculating%2Bthe%2Bnumber%2Bneeded%2Bto%2Btreat%2Bfor%2Btrials%2Bwhere%2Bthe%2Boutcome%2Bis%2Btime%2Bto%2Ban%2Bevent%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.319.7223.1492%26rft_id%253Dinfo%253Apmid%252F10582940%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjEzOiIzMTkvNzIyMy8xNDkyIjtzOjQ6ImF0b20iO3M6MjM6Ii9ibWovMzQwL2Jtai5jMjE5Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-46-1\u0022 title=\u0022View reference 46 in text\u0022 id=\u0022ref-46\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.46\u0022 data-doi=\u002210.1001\/archinte.164.2.146\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EBauer DC, Mundy GR, Jamal SA, Black DM, Cauley JA, Ensrud KE, et al. Use of statins and fracture: results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EArch Intern Med\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2004\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E164\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E146\u003C\/span\u003E-52.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DArchives%2Bof%2BInternal%2BMedicine%26rft.stitle%253DArch%2BIntern%2BMed%26rft.issn%253D0003-9926%26rft.aulast%253DBauer%26rft.auinit1%253DD.%2BC.%26rft.volume%253D164%26rft.issue%253D2%26rft.spage%253D146%26rft.epage%253D152%26rft.atitle%253DUse%2Bof%2BStatins%2Band%2BFracture%253A%2BResults%2Bof%2B4%2BProspective%2BStudies%2Band%2BCumulative%2BMeta-analysis%2Bof%2BObservational%2BStudies%2Band%2BControlled%2BTrials%26rft_id%253Dinfo%253Adoi%252F10.1001%252Farchinte.164.2.146%26rft_id%253Dinfo%253Apmid%252F14744837%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1001\/archinte.164.2.146\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=14744837\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000188652600004\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-47-1\u0022 title=\u0022View reference 47 in text\u0022 id=\u0022ref-47\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.47\u0022 data-doi=\u002210.1007\/s10654-009-9396-x\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EBonovas S, Nikolopoulos G, Filioussi K, Peponi E, Bagos P, Sitaras NM. 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Long-term use of statins and risk of colorectal cancer: a population-based study. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EAm J Gastroenterol\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2009\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E104\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E3015\u003C\/span\u003E-23.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DThe%2BAmerican%2Bjournal%2Bof%2Bgastroenterology%26rft.stitle%253DAm%2BJ%2BGastroenterol%26rft.aulast%253DSingh%26rft.auinit1%253DH.%26rft.volume%253D104%26rft.issue%253D12%26rft.spage%253D3015%26rft.epage%253D3023%26rft.atitle%253DLong-term%2Buse%2Bof%2Bstatins%2Band%2Brisk%2Bof%2Bcolorectal%2Bcancer%253A%2Ba%2Bpopulation-based%2Bstudy.%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fajg.2009.574%26rft_id%253Dinfo%253Apmid%252F19809413%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1038\/ajg.2009.574\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=19809413\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000272553100020\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-49-1\u0022 title=\u0022View reference 49 in text\u0022 id=\u0022ref-49\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.49\u0022 data-doi=\u002210.1016\/S0002-9149(02)02355-X\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ETolman KG. The liver and lovastatin. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EAm J Cardiol\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2002\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E89\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E1374\u003C\/span\u003E-80.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DThe%2BAmerican%2Bjournal%2Bof%2Bcardiology%26rft.stitle%253DAm%2BJ%2BCardiol%26rft.aulast%253DTolman%26rft.auinit1%253DK.%2BG.%26rft.volume%253D89%26rft.issue%253D12%26rft.spage%253D1374%26rft.epage%253D1380%26rft.atitle%253DThe%2Bliver%2Band%2Blovastatin.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0002-9149%252802%252902355-X%26rft_id%253Dinfo%253Apmid%252F12062731%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=10.1016\/S0002-9149(02)02355-X\u0026amp;link_type=DOI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\u0022\u003E\u003Cspan\u003ECrossRef\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=12062731\u0026amp;link_type=MED\u0026amp;atom=%2Fbmj%2F340%2Fbmj.c2197.atom\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-medline\u0022\u003E\u003Cspan\u003EPubMed\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/external-ref?access_num=000176247900008\u0026amp;link_type=ISI\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\u0022\u003E\u003Cspan\u003EWeb of Science\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-50-1\u0022 title=\u0022View reference 50 in text\u0022 id=\u0022ref-50\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.50\u0022 data-doi=\u002210.1002\/pds.1603\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003EGarc\u00eda-Rodr\u00edguez LA, Mass\u00f3-Gonz\u00e1lez EL, Wallander M-A, Johansson S. 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Cataract and the use of statins: a case-control study. \u003Cabbr class=\u0022cit-jnl-abbrev\u0022\u003EQ J Med\u003C\/abbr\u003E\u003Cspan class=\u0022cit-pub-date\u0022\u003E2003\u003C\/span\u003E;\u003Cspan class=\u0022cit-vol\u0022\u003E96\u003C\/span\u003E:\u003Cspan class=\u0022cit-fpage\u0022\u003E337\u003C\/span\u003E-43.\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003Ca href=\u0022{openurl}?query=rft.jtitle%253DQJM%26rft.stitle%253DQJM%26rft.issn%253D0033-5622%26rft.aulast%253DSmeeth%26rft.auinit1%253DL.%26rft.volume%253D96%26rft.issue%253D5%26rft.spage%253D337%26rft.epage%253D343%26rft.atitle%253DCataract%2Band%2Bthe%2Buse%2Bof%2Bstatins%253A%2Ba%2Bcase-control%2Bstudy%26rft_id%253Dinfo%253Adoi%252F10.1093%252Fqjmed%252Fhcg064%26rft_id%253Dinfo%253Apmid%252F12702782%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-openurl cit-ref-sprinkles-open-url\u0022\u003E\u003Cspan\u003EOpenUrl\u003C\/span\u003E\u003C\/a\u003E\u003Ca href=\u0022\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NToicWptZWQiO3M6NToicmVzaWQiO3M6ODoiOTYvNS8zMzciO3M6NDoiYXRvbSI7czoyMzoiL2Jtai8zNDAvYm1qLmMyMTk3LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==\u0022 class=\u0022cit-ref-sprinkles cit-ref-sprinkles-ijlink\u0022\u003E\u003Cspan\u003E\u003Cspan class=\u0022cit-reflinks-abstract\u0022\u003EAbstract\u003C\/span\u003E\u003Cspan class=\u0022cit-sep cit-reflinks-variant-name-sep\u0022\u003E\/\u003C\/span\u003E\u003Cspan class=\u0022cit-reflinks-full-text\u0022\u003E\u003Cspan class=\u0022free-full-text\u0022\u003EFREE \u003C\/span\u003EFull Text\u003C\/span\u003E\u003C\/span\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003Cli\u003E\u003Ca class=\u0022rev-xref-ref\u0022 href=\u0022#xref-ref-52-1\u0022 title=\u0022View reference 52 in text\u0022 id=\u0022ref-52\u0022\u003E\u21b5\u003C\/a\u003E\u003Cdiv class=\u0022cit ref-cit ref-journal\u0022 id=\u0022cit-340.may19_4.c2197.52\u0022 data-doi=\u002210.1136\/bmj.b81\u0022\u003E\u003Cdiv class=\u0022cit-metadata\u0022\u003E\u003Ccite\u003ETannen RL, Weiner MG, Xie D. 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Individualising the risks of statins in men and women in England and Wales: population based cohort study using the QResearch database. \u003Cspan class=\u0022cit-source\u0022\u003EHeart\u003C\/span\u003E [forthcoming].\u003C\/cite\u003E\u003C\/div\u003E\u003Cdiv class=\u0022cit-extra\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/li\u003E\u003C\/ol\u003E\u003C\/div\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022https:\/\/www.bmj.com\/content\/340\/bmj.c2197.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022\u003EView Abstract\u003C\/a\u003E\u003C\/div\u003E \u003C\/div\u003E\n\n \n \u003C\/div\u003E\n\u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript src=\u0022https:\/\/www.bmj.com\/sites\/default\/files\/js\/js_am8GAfrhW3uXc7HVCmqF3MltMmNunvhyJ6MM_6EffRE.js\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}